Compositions for reducing hair loss and/or increasing hair regrowth

ABSTRACT

The invention relates to a composition comprising 2% to 5% minoxidil, 0.01% to 15% of a 5α-reductase inhibitor or an androgen receptor antagonist, and 0.01% to 15% of a prostaglandin analogue. In one embodiment, the prostaglandin analogue is latanoprost. In a preferred embodiment, the composition comprises 5% minoxidil, 0.1% finasteride and 0.03% latanoprost. The invention also relates to the use of the said composition to reduce hair loss and/or increase regrowth of hair in a human subject.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. patent applicationSer. No. 14/917,501, which is a continuation of PCT/CA2015/000327 filedMay 22, 2015 which in turn claims priority to US provisional patentapplication 62/002,397, filed May 23, 2014, this application also claimspriority to Canadian Patent Application Ser. No. 2903734, filed Sep. 2,2015. The disclosure of the above applications are hereby incorporatedherein by reference.

FIELD OF INVENTION

The inventor has developed a composition comprising minoxidil,finasteride and a prostaglandin analogue that shows improved propertiesin terms of reducing hair loss and increasing hair regrowth whencompared to conventional therapies, such as the topical application of asolution of 5% minoxidil.

BACKGROUND

Androgenetic alopecia (AGA) is hair loss (at scalp level) caused by thethinning of hair follicles. It is very common in men between the age of19 and 70 years. Notably, more than 50% of Caucasian men in theirfifties are affected by it. Women's hair loss mostly becomes an issueafter menopause.

Alopecia occurs as a result of the transformation of terminal hairfollicles, which are large, thick and pigmented, to vellus hairfollicles, which are short, thin and non-pigmented. This process isknown as miniaturization. Dihydrotestoterone (DHT) is believed to play arole in such a process. Testosterone is converted to DHT in the cells bythe enzyme, 5α-reductase. This enzyme is found in various tissuesincluding the hair follicle. Decreasing the levels of DHT in the hairfollicle can prevent or slow down the miniaturization process. This canbe accomplished either by inhibiting the conversion of testosterone toDHT or by competing with testosterone or DHT for the androgen receptorsthrough the use of an androgen receptor antagonist.

Individuals affected by androgenetic alopecia (AGA) show a diminution oftheir self-esteem that can effect negatively many facets of their lives.The inventor has developed a composition for topical administrationcomprising minoxidil, finasteride and a prostaglandin analogue iseffective in reducing hair loss and increasing hair regrowth.

There are several hair loss prevention products on the market. By way ofexample, minoxidil has been in use since the 1990s in topical form at 2%concentration (without prescription) and at 3% and 5% concentration(with prescription). While studies demonstrate the efficiency of 5%minoxidil over the 2% concentration, minoxidil is less than 40%effective in promoting regrowth of the hair. Minoxidil is considered thetopical gold standard available for treatment of hair loss.

Another hair loss prevention product is finasteride. It is administeredorally usually at a dosage of 1 mg/day. There are a number of sideeffects associated with the administration of finasteride includinglowered libido, impotence, ejaculation disorders, allergic reactions,testicular pain, male infertility, male breast cancer and depression. Athigher concentrations (5 mg), finasteride can cause benign prostatehyperplasia.

Latanoprost, a PGF_(2α) prostaglandin analog, is widely used inophthalmology to treat open angle glaucoma and ocular hypertension. Oneof its side effects has been an augmentation of periocular hirsuteness,which includes a surge in the thickness, length and pigmentation ofeyelashes which is to be distinguished from hair growth. Some of itsother adverse effects are erythema, folliculitis, sensation of burningand erysipelas. A latanoprost ophthalmic solution has a concentration of0.005%. It should be noted that scalp hair follicles and eyelashfollicles are not identical and one cannot simply extrapolate from adrug effect on one type of hair to another.

SUMMARY

The inventor has developed a composition comprising minoxidil, either a5α-reductase inhibitor or an androgen receptor antagonist, and aprostaglandin analogue for topical application to the scalp reduces hairloss and increases hair regrowth. Such a composition shows superiorimprovements to those seen for each of the components of the compositiontaken individually and the results obtained to date suggest that theimprovements may be superior to those of the sum of the said components.

The invention relates to a composition comprising 2% to 5% minoxidil,0.01% to 15% of a 5α-reductase inhibitor or an androgen receptorantagonist, and 0.01% to 15% of a prostaglandin analogue.

In a preferred embodiment, the invention relates to a compositioncomprising 2% to 5% minoxidil, 0.01% to 15% finasteride and 0.01% to 15%of a prostaglandin analogue. In one embodiment, the prostaglandinanalogue is latanoprost. In another embodiment, the compositioncomprises 5% minoxidil, 0.1% finasteride and 0.03% latanoprost. Theinvention also relates to the use of a composition comprising 2% to 5%minoxidil, 0.01% to 15% finasteride and 0.01% to 15% of a prostaglandinanalogue to reduce hair loss and/or increase regrowth of hair in a humansubject.

BRIEF DESCRIPTION OF THE FIGURES

FIGS. 1A to 1L are a series of photographs showing the scalp ofparticipant 1 prior treatment and at intervals throughout the course ofa six month treatment with a composition of the invention. FIGS. 1A and1B show the scalp before treatment on the first day of month 1, FIGS. 1Cand 1D show the scalp on month 2, FIGS. 1E and 1F on month 3, FIGS. 1Gand 1H on month 4, FIGS. 1I and 1J on month 5 and FIGS. 1K and 1L onmonth 6;

FIGS. 2A to 2L are a series of photographs showing the scalp ofparticipant 2 prior to treatment and at intervals throughout the courseof a six month treatment with a composition of the invention. FIGS. 2Aand 2B show the scalp before treatment on the first day of month 1,FIGS. 2C and 2D show the scalp on month 2, FIGS. 2E and 2F on month 3,FIGS. 2G and 2H on month 4, FIGS. 2I and 2J on month 5 and FIGS. 2K and2L on month 6;

FIGS. 3A to 3L are a series of photographs showing the scalp ofparticipant 3 prior to treatment and at intervals throughout the courseof a six month treatment with a composition of the invention. FIGS. 3Aand 3B show the scalp before treatment on the first day of month 1,FIGS. 3C and 3D show the scalp on month 2, FIGS. 3E and 3F on month 3,FIGS. 3G and 3H on month 4, FIGS. 3I and 3J on month 5 and FIGS. 3K and3L on month 6;

FIGS. 4A to 4L are a series of photographs showing the scalp ofparticipant 4 prior to treatment and at intervals throughout the courseof a six month treatment with a solution of 5% minoxidil only. FIGS. 4Aand 4B show the scalp before treatment on the first day of month 1,FIGS. 4C and 4D show the scalp on month 2. FIGS. 4E and 4F on month 3,FIGS. 4G and 4H on month 4, FIGS. 4I and 4J on month 5 and FIGS. 4K and4L for month 6;

FIGS. 5A to 5L are a series of photographs showing the scalp ofparticipant 5 prior to treatment and at intervals throughout the courseof a six month treatment with a solution of 0.1% finasteride only. FIGS.5A and 5B show the scalp before treatment on the first day of month 1,FIGS. 5C and 5D show the scalp on month 2, FIGS. 5E and 5F on month 3,FIGS. 5G and 5H on month 4, FIGS. 5I and 5J on month 5 and FIGS. 5K and5L on month 6;

FIGS. 6A to 6L are a series of photographs showing the scalp ofparticipant 6 prior to treatment and at intervals throughout the courseof a six month treatment with a solution of 0.1% finasteride only. FIGS.6A and 6B show the scalp before treatment on the first day of month 1,FIGS. 6C and 6D show the scalp on month 2, FIGS. 6E and 6F 6C on month3, FIGS. 6G and 6H on month 4, FIGS. 6I and 6J on month 5 and FIGS. 6Kand 6L on month 6;

FIGS. 7A to 7G are a series of photographs showing the scalp ofparticipant 7 prior to treatment and at intervals throughout the courseof a six month treatment with a solution of 0.1% finasteride only. FIGS.7A and 7B show the scalp before treatment on the first day of month 1,FIG. 7C shows the scalp on month 2, FIG. 7D on month 3, FIG. 7E on month4, FIG. 7F on month 5 and FIG. 7G on month 6;

FIGS. 8A to 8L are a series of photographs showing the scalp ofparticipant 8 prior to treatment and at intervals throughout the courseof a six month treatment with a solution of 0.1% finasteride only. FIGS.8A and 8B show the scalp before treatment on the first day of month 1,FIGS. 8C and 8D show the scalp on month 2, FIGS. 8E and 8F on month 3,FIGS. 8G and 8H on month 4, FIGS. 8I and 8J on month 5 and FIGS. 8K and8L on month 6;

FIGS. 9A to 9L are a series of photographs showing the scalp ofparticipant 9 prior to treatment and at intervals throughout the courseof a six month treatment with a solution of 0.03% latanoprost only.FIGS. 9A and 9B show the scalp before treatment on the first day ofmonth 1. FIGS. 9C and 9D show the scalp on month 2, FIGS. 9E and 9F onmonth 3. FIGS. 9G and 9H on month 4, FIGS. 9I and 9J on month 5 andFIGS. 9K and 9L on month 6;

FIGS. 10A to 10L are a series of photographs showing the scalp ofparticipant 10 prior to treatment and at intervals throughout the courseof a six month treatment with a solution of 0.03% latanoprost only.FIGS. 10A and 10B show the scalp before treatment on the first day ofmonth 1, FIGS. 10C and 10D show the scalp on month 2, FIGS. 10E and 10Fon month 3, FIGS. 10G and 10H on month 4, FIGS. 10I and 10J on month 5and FIGS. 10K and 10L on month 6.

DETAILED DESCRIPTION OF THE INVENTION

The invention relates to a composition comprising minoxidil, a5α-reductase inhibitor or an androgen receptor antagonist and aprostaglandin analog which shows improved properties for the reductionof hair loss and for the increase of hair regrowth in human subjects,when compared to each component taken alone.

Minoxidil or (6-(1-pipedidinyl)-2,4-pyrimidinediamine 3-oxide) has thefollowing structural formula:

Minoxidil is a crystalline solid which has a solubility in mg/ml of 75in propylene glycol, of 44 in methanol, of 29 in ethanol, of 6.7 in2-propanol, of 6.5 in DMSO, of 2.2 in water, of 0.5 in chloroform, andof <0.5 in acetone. Minoxidil has a pKa of 4.61.

Inhibitors of 5α-reductase inhibit the conversion of testosterone toDHT. The 5α-reductase enzyme has three different isoforms, type I, typeD or type III. The inhibitors can inhibit one or more of the theseisoforms. The type II form is found predominantly in the hair follicles.Finasteride is an example of a 5α-reductase type II and III inhibitor.While the composition tested comprises finasteride, it is hypothesizedthat other 5α-reductase inhibitors can also be used. By way of example,other suitable 5α-reductase inhibitors include dutasteride ((5α,17β)-N-{2,5-Bis(trisfluoromethyl)phenyl}-3-oxo-4-azaandrost-1-ene-17-carboxamide),izonsteride((4aR,10bR)-8-[(4-ethyl-1,3-benzothiazol-2-yl)sulfanyl]-4,10b-dimethyl-1,4,4a,5,6,10b-hexahydrobenzo[f]quinolin-3(2H)-one), epristeride(17-(tert-butylcarbamoyl)androsta-3,5-diene-3-carboxylic acid),lapisteride(N-[1-(4-methoxyphenyl)-1-methylethyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide),turosteride((4aR,4bS,6aS,7S,9aS,9bS,11aR)-1,4a,6a-trimethyl-2-oxo-N-(propan-2-yl)-N-(propan-2-ylcarbamoyl)hexadecahydro-1H-indeno[5,4-f]quinoline-7-carboxamide)and alfatradiol (Estra-1,3,5(10)-triene-3,17α-diol). Duasteride is aninhibitor of all three forms of 5α-reductase. Lapisteride andizonsteride are types I and II inhibitors. Epristeride and turosterideare type II inhibitors.

Finasteride or((5α,17β)-N-(1,1-Dimethylethyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide)is an example of a 5α-reductase inhibitor and has the followingstructural formula:

Finasteride is conventionally administered orally at a daily dose of 1mg.

Finasteride is an anhydrous crystalline solid. Finasteride is freelysoluble in chloroform, DMSO, ethanol, methanol, n-propanol; sparinglysoluble in propylene glycol, polyethylene glycol 400; and very slightlysoluble in 0.1N HCl and 0.1N NaOH. Finasteride is not soluble in water.

Antagonists of the androgen receptors work by competing withtestosterone and DHT for androgen receptor binding leading to reducedlevels of DHT. Various antagonists of the androgen receptors are known.By way of example, these include flutamide(2-methyl-N-[4-nitro-3-(trifluoromethy))phenyl]-propanamide) andtopilutamide(2-Hydroxy-2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]-3-[2,2,2-trifluoroacetyl)amino]propanamide),which is also known as fluridil. It is surmised that while the androgenreceptor antagonists have a different mechanism of action than the5α-reductase inhibitors, they share a common effect of leading todecreased levels of DHT in the hair follicle and thus could be used inthe hair composition of the invention.

Latanoprost or((5Z)-7-[(1R,2R,3R,5SO-3,5-Dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-5-heptenoic acid 1-methylethyl ester) has the followingstructural formula:

Latanoprost is an oil. Latanoprost is very soluble in acetonitrile;freely soluble in acetone, ethanol, ethyl acetate, isopropanol, methanoland octanol. It is practically insoluble in water.

Prostaglandins regulate a number of physiological functions. It has beenfound that most hair cell types are endowed with prostaglandinmetabolism machinery and are thus able to produce PGE₂ and/or PGF_(2α).The epithelial part of the hair bulb is the main source of prostaglandinsynthesis and interconversion. From Colombe et al. (ProstaglandinMetabolism in Human Hair Follicle, Exp Dermatol. 2007 September, 16(9):762 to 769) and as minoxidil has also been found to enhanceprostaglandin endoperoxide synthase-1 (PGHS-1) activity, this suggeststhat prostaglandins are involved in hair growth and differentiationcontrol and that there is a link between prostaglandin synthesis andhair growth. Minoxidil has been demonstrated to be a potent activator ofpurified PGHS-1 by assaying oxygen consumption in prostaglandin PGE₂production suggesting that the mechanism beyond the hair-growthstimulating effect of minoxidil is stimulation of PGE₂ synthesis(Michelet et al., Activation of Cytoprotected Prostaglandin Synthase-1by Minoxidil as a Possible Explanation for Its Hair Growth-StimulatingEffect, J. Invest Dermatol 1997: 108: 205-209). This has been confirmedby the role of PGHS-2 in the control of hair cycle (Muller-Decker etal., Expression of Cyclo-Oxygenase Isozymes During Morphogenesis andCycling of Telage Hair Follicles in Mouse Skin, J. Invest Dermatol 2003:121: 661-668). It has been shown that the human hair follicle cansustain a complete PGE₂ and PGF_(2α) metabolism. Human hair follicleexpress (i) mPGES-1, mPGES-2 and cPGES which catalyse PGE₂ synthesisfrom PGH₂, (ii) AKR1C3/PGFS which converts PGH₂ into PGF_(2α) and (iii)CDR1 and AKR1C1 aldo-ketoreductase, which could control PGE₂/PGF_(2α)interconversion. As such, it has been shown that human hair folliclesappear fully enzymatically equipped to self-process prostaglandinsynthesis and metabolism, meaning PGE₂ and PGF_(2α) could be producedand inter-converted by hair follicles. While the composition testedcomprised latanoprost, a PGF_(2α) prostaglandin analogue, it is surmisedthat other prostaglandin analogues can also be used given the roleplayed by prostaglandin in hair growth and differentiation. By way ofexample, other suitable prostaglandin analogues include travoprost,bimatoprost, tafluprost and unoprostone.

The composition of the invention comprises 2% to 5% minoxidil, 0.01% to15% of a 5α-reductase inhibitor of an androgen receptor antagonist and0.01% to 15% of a prostaglandin analogue. In a preferred embodiment, thecomposition comprises 2% to 5% minoxidil, 0.01% to 5% finasteride and0.01% to 5% of a prostaglandin analogue. In a more preferred embodiment,the composition comprises 5% minoxidil, 0.5% finasteride and 0.1% of aprostaglandin analogue. In a yet other preferred embodiment, theprostaglandin analogue is latanoprost, travoprost, bimatoprost,tafluprost or unoprostone. In a further preferred embodiment, theprostaglandin analogue is latanoprost. In an even more preferredembodiment, the composition comprises 5% minoxidil, 0.1% finasteride and0.03% latanoprost as set out in Table 1 below.

In order to demonstrate the improved properties of a compositionsuitable for topical application comprising minoxidil, finasteride and aprostaglandin analogue, latanoprost, the composition was compared tocompositions comprising 5% minoxidil only, 0.1% finasteride only and0.03% latanoprost only. The various compositions were prepared asfollows.

Example 1 Preparation of Composition Comprising Finasteride, Latanoprostand Minoxidil

In order to prepare the composition, latanoprost was diluted to obtain aconcentration of 10,000 mcg/ml of solute on in absolute ethyl alcohol,and prepared as a stock solution and kept in a freezer to enhancestability (−20° C.). Absolute ethyl alcohol was mixed with propyleneglycol and heated to 55°-65° C. Minoxidil powder was then added to thealcohol/propylene glycol mixture. In a containment hood, finasteride wasadded to the solution and stirred until dissolved. The preparation wascooled to room temperature. Ethoxy diglycol and latanoprost were addedto the cooled solution and stirred well, until in solution. The finalsolution was brought to volume with absolute ethyl alcohol.

The amounts used are set out in Table 1 below:

Component Function Quantity per unit % Propylene glycol Solvent 30 ml 50Minoxidil USP Active 3 g 5 Finasteride USP Active 0.06 g 0.1 Ethoxydiglycol reagent Solvent 3 ml 5 Latanoprost (10,000 mcg/ml) Active 1.8ml 0.03 Absolute ethyl alcohol Solvent QS 60 ml 39.87 TOTAL 60 ml 100%

Various modifications for the preparation of the composition of theinvention will be apparent to the skilled worker. Furthermore, otherpharmaceutically acceptable additives such as suspending agents,emulsifying agents, non-aqueous vehicles and preservatives can be added.The techniques for the preparation of these compositions are well knownin the art and reference may be had to Remington's PharmaceuticalSciences, 18^(th) edition, Mack Publishing Co., Easton, Pa., USA 18042.

Example 2 Preparation of Composition Comprising Minoxidil

A composition comprising 5% minoxidil was prepared. Absolute ethylalcohol was mixed with propylene glycol and heated to 55° to 65° C. Theminoxidil powder was added to the alcohol/propylene glycol mixture.Ethoxy diglycol was added and the solution was stirred. The finalsolution was brought to volume with absolute ethyl alcohol to obtain asolution comprising 5% minoxidil.

Example 3 Preparation of Composition Comprising Finasteride

A composition comprising 0.1% finasteride was also prepared. Absoluteethyl alcohol was mixed with propylene glycol. Finasteride was added tothe alcohol/propylene glycol mixture to obtain a solution having aconcentration of 0.1% finasteride. Absolute ethyl alcohol also servesthe function of preservative.

Example 4 Preparation of Composition Comprising Latanoprost

A solution comprising 0.03% latanoprost was prepared. Absolute ethylalcohol was mixed with propylene glycol. The latanoprost was added tothe alcohol/propylene glycol mixture. The final solution was brought tovolume with absolute ethyl alcohol in order to obtain a solution havinga concentration of 0.03% latanoprost. The absolute ethyl alcohol alsoserves the function of preservative in this composition.

Example 5 Treatment of Participants with Composition of Invention andComparators—Analysis and Measurements

For each participant, the distance between the base of the nose and themiddle of the hair crown was noted, as well as the distance separatingthe most distal part of the helix and the hair crown. A square area oftwo centimeters by two centimeters was measured around the middle pointof the hair crown (marked by a washable felt crayon). Photographs weretaken of each participant's scalp.

The participants were seen at monthly intervals over a six-month periodand their hair was analysed in the manner described above andphotographs taken.

Results

A. Treatment with Composition Comprising Finasteride, Latanoprost andMinoxidil

Each participant first had his hair analysed as described above andphotographs taken. Following the first analysis, each participant wasprovided with a solution comprising 0.1% finasteride, 0.03% latanoprostand 5% minoxidil prepared as described in Example 1 above. Theparticipants applied 1 ml to the scalp, once a day after cleansing. The1 ml was applied as 10 metered dose sprays of 0.1 ml.

The results for three participants are provided. Participant 1 was amale of 61 years of age (FIG. 1 ). Participant 2 was a male of 23 yearsof age (FIG. 2 ) while participant 3 was a male of 29 years of age (FIG.3 ). All three participants had androgenetic alopecia, as did theparticipants of the comparator groups.

FIGS. 1, 2 and 3 clearly show a marked decrease of hair loss and anincrease in hair regrowth in all three participants.

B. Comparison with Treatment with Minoxidil, Finasteride and LatanoprostAlone

Each participant first had his hair analysed as described in part Aabove and photographs taken. Following the first analysis, eachparticipant was provided with a solution comprising either 5% minoxidil,0.1% finasteride, or 0.03% latanoprost. The compositions were preparedas described in Examples 2 to 4 above. The participants applied 1 ml tothe scalp, once a day after cleansing. The 1 ml was applied as 10metered dose sprays of 0.1 ml.

The results for the participants of each group are provided.

The participant for the minoxidil group was a 64 year old male. FIG. 4shows the results obtained for this participant. Only a slightimprovement in hair regrowth is observed and the results are veryinferior to those seen with the composition of the invention.

Four participants used a solution of 0.1% finasteride only. Theseparticipants were respectively 30 (participant 5), 33 (participant 6),36 (participant 7) and 46 years of age (participant 8). FIGS. 5, 6, 7and 8 show the results for participants 5, 6, 7 and 8 respectively. Onlya slight improvement in hair regrowth is observed. The results are farinferior to those seen with the composition of the invention.

Two participants used a solution comprising 0.03% latanoprost only.These participants were respectively 48 (participant 9) and 52(participant 10) years of age. FIGS. 9 and 10 show the results forparticipants 9 and 10 respectively. Only a slight improvement in hairregrowth was observed. The results obtained are far inferior to thoseobserved with the composition of the invention.

The composition comprising minoxidil, finasteride and latanoprost showsimproved properties in terms of reduction of hair loss and increase ofregrowth of hair when compared to a solution of 5% minoxidil alone, asolution of 0.1% finasteride alone or a solution of 0.03% latanoprostalone. The improvements shown in the reduction of hair loss and theincrease of regrowth hair for the composition of the invention aresuperior to the improvements seen for each of the components of thecomposition taken individually and the results obtained to date suggestthat the improvements may be superior to those of the sum of the saidcomponents.

While the composition of the invention has been tested on males, similarresults are expected on females as the mechanism of hair growth is thesame for both genders.

While a composition of the invention comprising a specific 5α-reductaseinhibitor, namely finasteride, has been tested, it is surmised thatother 5α-reductase inhibitors, will work in the same manner asfinasteride. Inhibitors of form II of 5α-reductase are most preferred asthe type II form of 5α-reductase is found predominantly in the hairfollicles. It is also surmised that androgen receptor antagonists havean effect similar to that of finasteride in that they would lead to adecrease in the levels of DHT.

While the present invention has been described in connection withspecific embodiments thereof and in a specific use, variousmodifications will occur to those skilled in the art. The scope of theclaims should not be limited by the preferred embodiments or theexamples but should be given the broadest interpretation consistent withthe description as a whole.

What is claimed is:
 1. A topical composition, comprising: (a) 2% to 5%minoxidil; (b) finasteride in an amount greater than or equal to 0.01%and less than 0.225%; and (c) 0.01% to 0.15% latanoprost, wherein thetopical composition is for topical application to a scalp.
 2. Thecomposition according to claim 1, wherein the composition comprises atleast 0.05% finasteride.
 3. The composition according to claim 1,wherein the composition comprises 0.03% to 0.15% latanoprost.
 4. Thecomposition according to claim 1, wherein the composition comprises 3%to 5% minoxidil.
 5. A composition for use in reducing hair loss orincreasing regrowth of hair in a human subject, the compositioncomprising: (a) 2% to 5% minoxidil; (b) finasteride in an amount greaterthan or equal to 0.01% and less than 0.225%; and (c) 0.01% to 0.15%latanoprost.
 6. The composition according to claim 5, wherein thecomposition comprises at least 0.05% finasteride.
 7. The compositionaccording to claim 5, wherein the composition comprises 0.03% to 0.15%latanoprost.
 8. The composition according to claim 5, wherein thecomposition comprises 3% to 5% minoxidil.
 9. The composition accordingto claim 5, wherein the human subject is a male.
 10. The compositionaccording to claim 5, wherein the human subject is a female.
 11. Thecomposition according to claim 5, wherein said composition is fortopical administration.
 12. The composition according to claim 11,wherein the composition is in the form of a spray.
 13. The compositionof claim 1, wherein the composition is in the form of a spray.